Process for evaluating a property of a discrete plurality of chemical substances



Aug. 11, 1970 H. LOEBL ,7

PROCESS FOR EVALUATING A PROPERTY OF A DISCRETE PLURALITY OF CHEMICAL SUBSTANCES Filed May 5, 1966 INVENTOR:

Haessz, Z L OEBL United States Patent "ice US. Cl. 23-230 2 Claims ABSTRACT OF THE DISCLOSURE Method of processing a plurality of samples wherein the samples are placed in a plurality of discrete containers, transferred by means of a pipette or the like to a second plurality of discrete containers located in a holder together with the addition of a predetermined quantity of at least one reagent which is mixed with the samples. The samples are then transferred in discrete containers to a treatment station, such as a centrifuging station, and then transferred in the discrete containers to a photometric measuring instrument, in which a recording pen is held stationary between sample tests, and for a period of time after the sample is transferred to the instrument, for evaluating a property of each sample.

Our invention is concerned with a discrete process for automatically evaluating a property such as the colour or density of a plurality of chemical substances such as biochemical samples.

In institutions such as hospitals it is often required to ascertain rapidly the colour, density or concentration of a plurality of similar samples of prepared body fluids. In this connection it is known to locate the said samples as separate globules in a transparent tube, the globules being separated by bubbles of air or cleaning fluid, and to pass the said samples in a continuous flow through the photometer for evaluation of, for example, the colour density of each sample. This process has a number of disadvantages one of which is that as all the samples flow through a single tube, they tend to contaminate one another. In addition, since only one channel for the said solutions to the photometer is provided, the latter, which is the most expensive part of the apparatus, is not used to its fullest extent, since the photometer can act more rapidly than the remainder of the apparatus.

According to our invention, in a discrete process for evaluating a property of a plurality of chemical substances such as biochemical samples, the samples are placed in sequence in a first plurality of containers, a measured quantity from each sample is transferred automatically by one or more pipettes to a second plurality of containers located in a holder, together with the addition of a predetermined quantity of one or more reagents which are mixed with the samples, whereafter the prepared samples, with or without passage through treatment stages such as heating or centrifuging are manually transferred sequentially to an automatically operated measuring instrument which evaluates and displays or records a particular property of each of the said samples.

In one embodiment of our invention, body fluid samples of the same kind are collected from a plurality of patients, in labelled tubes, the said tubes being placed in a circular container adapted to hold a plurality of 3,523,756 Patented Aug. 11, 1970 such tubes. A similarly shaped container having a plurality of sample receptacles is located near the first on a rotary support, and the two are rotated at the same angular speed. As each sample tube passes a transfer position, a pipette is caused to dip in the sample, suck up a predetermined quantity, transfer it to a receptacle and add a quantity of reagent or cleaning fluid which removes substantially all traces of the sample from the pipette.

The second container, which may be suitable for mounting in a centrifuge, is then manually conveyed thereto, and components such as proteins settled out. Thereafter the container is replaced on a rotary support, and the fluid in the receptacles, with or without further treatment, is transferred sequentially to an automatic photometer. A further pipette extracts each sample in turn from its receptacle and transfers it to a cuvette located in the photometer, which automatically evaluates a property such as the colour density of the sample, whereafter the cuvette is washed out and a further sample transferred to it. Alternatively the sample may be transferred to a plurality of cuvettes which are passed in sequence through the photometer and thereafter washed out.

The photometer may either draw a graph the height of which shows the required value of the sample, it may cause a display of the measured quantity in the form of a number, or it may print the said number, together with another number representative of the particular sample under test. Alternatively or additionally, the photometer may punch a card or tape for later statistical evaluation.

Numerous modifications may be made to the process outlined above. Thus, instead of the fluid in the second receptacle being transferred directly to the photometer, a second transfer of samples may be effected for the addition of a further reagent.

As regards the photometer, this is preferably of the comparator type, in which the colour or density measurement of the sample is compared by the photometer with a standard light beam, the latter having an automatically adjusted graduated wedge inserted in it. Movement of the wedge until equivalence of light from the sample and from the wedge occurs, sets the numerical portion of the photometer so as'to permit display, printing or punching of a signal corresponding to the sample being tested.

The process described above is particularly advantageous in that since the photometer is the most expensive part of the chain of apparatus involved, and since it operates with greater rapidity, two or more channels of sample collection and preparation may be operated simultaneously, thus keeping the photometer fully occuplied. It is envisaged that a sample evaluation room housing the photometer could be employed, the remaining steps of the process being carried out in or near the various wards of the hospital. This simplifies the channelling of the process and avoids any possibility of error in the associateion of each sample reading with the samle concerned.

Reference should now be made to the accompanying drawing, which shows by way of example a complete set of treatment and evaluation steps as applied to biological fluid samples.

The steps are performed by four rigs and a photometer-' evaluator, numbered 1, 2, 3, 4 and 5 respectively. The apparatus of the rigs is more fully described in my copending US. patent application, Ser. No. 547,290, filed on May 3, 1966, and the photometer-evaluator in my copending US. patent application, Ser. No. 547,247, filed on May 3, 1966.

A set of biological fluid samples is collected from hospital patents in labelled tubes 6, and these are placed sequentially in an outer ring container 7. An inner ring 8 is furnished with a like number of empty receptacles such as 9 (rig 2) and the container and rig are located on a rotatable table 10 which is indexed from one tube position to the next by a pin-and-slot mechanism which drives the table, so that each pair of receptacles and tube remain opposite a predetermined position for a specified time. This start-stop movement continues until each such pair has been brought to and removed from the said position. Tongues on the table and slots in the container and ring ensure accurate location thereof with respect to one another.

As each tube and receptacle reach the said predetermined position, a pipette 11 mounted on a cam-moved arm 12 dips into a tube and by means of a pump 13 and flexible pipes 14, 15, extracts an amount of sample fluid determined by the pump throw. The pipette then withdraws and moves to the corresponding receptacle 9 on the inner ring whereupon the sample fluid is ejected together with the necessary quantity of reagent or cleaning fluid from the reservoir 16. After withdrawal of the pipette and its return to its previous position, the table revolves to the next position, and the cycle is repeated until diluted samples occupy all the receptacles. The ring is now removed by hand, and if necessary transferred to a centrifuge or even to promote clearing or reaction of the liquids.

The actions of the pipette and rotation of the table are effected by means of an electric motor individual to each rig. the motor having a camshaft and gearbox associated therewith but not shown. All the necessary gears, mountings, pump mechanisms and the like are carried in a housing 50.

After the centrifuging or other operation, mentioned above, the receptacle ring 8 may be returned to rig 2. This rig has a pipette mechanism 17 and table similar to rig 1, except that the pipette is guided so as to enter each receptacle 9 in turn and inject a measured quantity of a further reagent from a reservoir 18 by means of a pump 19, the table being indexted in a rotary manner meanwhile. This step in the process may be omitted if not required. More than one reagent may be added by the use of a multiple pump and reservoirs should this be necessary.

The inner ring 9 is now transferred to rig 3, and an outer ring 21 with empty tubes 22 is placed in position. The pipette 23, which is tilted and moves slantwise, moves into the first receptacle on ring 8 and by means of a pump 24 removes a quantity of the supernatant liquid therefrom and transfers it, free of sediment or deposited material and with or without a wash fluid, to a tube 22. The cycle continues until liquid has been removed and transferred from all the receptacles.

Rig. 4 is associated with the measuring device 5. When all the tubes 22 of ring 21 are filled, the ring and tubes are transferred to rig 4. Here a pipette 26 is adapted to dip in sequence into the tubes 22 which are index-rotated with respect to the pipette, a considerable quantity of fluid being extracted from each tube. This fluid passes via pipe 27 and pipe 29 to a sealed cuvette 30 located in the photometer 5. Vacuum applied by rig 4 from a pump (not shown) to pipe 31 sucks part of the said liquid from a tube 22 into the cuvette and then to a sump, this part being used to wash out the cuvette. A valve now closes to seal tube 31, and a lower vacuum applied to tube 28 fills the cuvette nearly full of the remainder of the fluid to be evaluated.

The photometer is of the comparator or double-beam type. The colour or density of the liquid in the cuvette is compared by means of a photocell which receives light alternately through the sample and through a graduated motor-operated wedge. The wedge is moved under control of the photocell until the two signals derived from the photocell are equal, whereupon a servo-motor operated pen 32 traces a line on a sheet of paper 33 moved beneath it. To avoid unnecessary or misleading movement of the pen its operation is timed to begin about 1 second after the liquid has been drawn into the cuvette, and the paper, until then stationary, moves for about 4 seconds, recording a substantially straight line the level of which corresponds to the density or colour of the sample being measured. The average level of the line is the actual measurement.

Simultaneously with this pen action, the mechanism of a digital print-out machine 34 may be actuated if this machine is provided, the machine printing a line of figures on a sheet of paper 34 giving digital information of the number of the sample, the number of the measurement and the value of the measurement, together with other particulars such as the date if required.

Although only a single reagent is shown as added in rigs 1 and 2, it is possible to add two or more reagents at each rig if required by the addition of reservoir, pipes, pumps and cam assemblies. Again, if different samples are to be evaluated, two or more pipettes with their reagent reservoirs may be provided at one or more rigs, a pipette previously in use being readily removed from its arm and replaced by another when a change is to be made. Finally, any one or more rigs may be omitted or added to the whole cycle described should this be desired; the cycle described is a normal and simple one, and it can be varied as required to suit the particular treatment steps and samples employed.

The process described can be carried out simultaneously in several channels if desired. Thus several pipettes may extract measured quantities simultaneously from one sample in say, a narrow trough, and transfer them, with the addition of different reagents, to separate receptacles so that different tests may be applied to the same sample fluids. Alternatively the said several pipettes may extract fluids from several different samples, and transfer them to different receptacles for subjection to the same test, this accelerating the sampling procedure. Two or more pipettes may add or subtract fluid sequentially to each receptacle during its passage through a particular rig. As shown in my copending U.S. patent application Ser. No. 547,290, the container or support for the sample tubes and receptacles may be a ring, single or multiple, a long straight table or an endless belt.

We claim:

1. A method for evaluating a property of a plurality of samples of chemical substances, and recording a representation thereof, comprising the steps:

placing said samples in sequence in a first plurality of' transferring said treated samples, sequentially, from the discrete containers, while the containers are in the holder, to a measuring cuvette; photometrically evaluating said property of each of said samples, in sequence; sequentially recording the results of said photometric evaluation by passing a pen recorder over a, paper strip to mark the paper strip; holding the pen stationary between sample tests, and causing said pen to write only after a predetermined period of time has passed after the filling of said cuvette wih said sample, said pen thereafter re-' maining on said paper for a further predetermined References Cited UNITED STATES PATENTS 7/1963 Skeggs 23-230 9/1964 Anthon 23-259 XR 6 3,178,266 4/1965 Anthon 23-259 XR 3,415,627 12/1968 Rait 23253 MORRIS O. WOLK, Primary Examiner 5 R. E. SERWIN, Assistant Examiner US. Cl. X.R. 

